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6-44403977-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001253.4(CDC5L):c.708C>T(p.Asp236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,612,186 control chromosomes in the GnomAD database, including 20,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2743 hom., cov: 32)
Exomes 𝑓: 0.12 ( 17742 hom. )

Consequence

CDC5L
NM_001253.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25
Variant links:
Genes affected
CDC5L (HGNC:1743): (cell division cycle 5 like) The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-44403977-C-T is Benign according to our data. Variant chr6-44403977-C-T is described in ClinVar as [Benign]. Clinvar id is 1228167.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.25 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDC5LNM_001253.4 linkuse as main transcriptc.708C>T p.Asp236= synonymous_variant 6/16 ENST00000371477.4
CDC5LXM_047419605.1 linkuse as main transcriptc.273C>T p.Asp91= synonymous_variant 2/12
POLR1CNM_001318876.2 linkuse as main transcriptc.946-37913C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDC5LENST00000371477.4 linkuse as main transcriptc.708C>T p.Asp236= synonymous_variant 6/161 NM_001253.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.152
AC:
23119
AN:
151712
Hom.:
2741
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.211
Gnomad AMI
AF:
0.0680
Gnomad AMR
AF:
0.124
Gnomad ASJ
AF:
0.114
Gnomad EAS
AF:
0.611
Gnomad SAS
AF:
0.349
Gnomad FIN
AF:
0.119
Gnomad MID
AF:
0.0949
Gnomad NFE
AF:
0.0836
Gnomad OTH
AF:
0.130
GnomAD3 exomes
AF:
0.170
AC:
42594
AN:
250284
Hom.:
6455
AF XY:
0.173
AC XY:
23434
AN XY:
135218
show subpopulations
Gnomad AFR exome
AF:
0.214
Gnomad AMR exome
AF:
0.121
Gnomad ASJ exome
AF:
0.114
Gnomad EAS exome
AF:
0.623
Gnomad SAS exome
AF:
0.317
Gnomad FIN exome
AF:
0.124
Gnomad NFE exome
AF:
0.0821
Gnomad OTH exome
AF:
0.140
GnomAD4 exome
AF:
0.119
AC:
173310
AN:
1460356
Hom.:
17742
Cov.:
32
AF XY:
0.123
AC XY:
89591
AN XY:
726382
show subpopulations
Gnomad4 AFR exome
AF:
0.212
Gnomad4 AMR exome
AF:
0.123
Gnomad4 ASJ exome
AF:
0.109
Gnomad4 EAS exome
AF:
0.576
Gnomad4 SAS exome
AF:
0.307
Gnomad4 FIN exome
AF:
0.122
Gnomad4 NFE exome
AF:
0.0835
Gnomad4 OTH exome
AF:
0.147
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.152
AC:
23141
AN:
151830
Hom.:
2743
Cov.:
32
AF XY:
0.160
AC XY:
11852
AN XY:
74178
show subpopulations
Gnomad4 AFR
AF:
0.211
Gnomad4 AMR
AF:
0.123
Gnomad4 ASJ
AF:
0.114
Gnomad4 EAS
AF:
0.611
Gnomad4 SAS
AF:
0.348
Gnomad4 FIN
AF:
0.119
Gnomad4 NFE
AF:
0.0836
Gnomad4 OTH
AF:
0.134
Alfa
AF:
0.0992
Hom.:
1281
Bravo
AF:
0.153
Asia WGS
AF:
0.476
AC:
1652
AN:
3478
EpiCase
AF:
0.0817
EpiControl
AF:
0.0790

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
8.9
Dann
Benign
0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6934058; hg19: chr6-44371714; COSMIC: COSV65176122; API